Background
Live donor liver transplantation (LDLT) mandates conversance in liver anatomy and major hepatectomy. Hepatocellular carcinoma is most reliably treated by hepatectomy.
Hypothesis
The outcomes of major hepatectomy for hepatocellular carcinoma are influenced by the surgeon's LDLT experience.
Design
We collected prospective cohort study data on patient and disease characteristics.
Setting
Tertiary referral center.
Patients
A retrospective study was performed on 250 patients who underwent major hepatectomy for hepatocellular carcinoma from January 16, 1996, through December 28, 2001.
Main Outcome Measures
Overall and disease-free survival and outcomes including blood loss, blood transfusion, and complications.
Results
The 3 liver transplantation surgeons (LTSs) performed 102 major hepatectomies; the 4 hepatobiliary and pancreatic surgeons (HBPSs), 148 major hepatectomies. Patients in both groups had similar baseline characteristics. The mean ± SD blood loss in the LTS and HBPS groups was 1.36 ± 1.37 and 2.21 ± 2.40 L, respectively (P<.001). The mean ± SD blood transfusion in the LTS and HBPS groups was 0.27 ± 0.82 and 0.51 ± 0.94 L, respectively (P = .001). Fewer patients in the LTS group required blood transfusion (17/102 [16.7%]; HBPS group, 57/148 [38.5%]; P<.001). We found no difference in overall and disease-free survival between the groups. The median overall survival was 55.8 months for the nontransfused group, and 34.3 months for the transfused group (P = .06). Median disease-free survival was 16.1 months for the nontransfused group compared with 12.4 months for the transfused group (P = .25). Cox regression multivariate analysis showed that transfusion, cirrhosis, and venous invasion worsened overall survival. Venous invasion, cirrhosis, and tumor size adversely affected disease-free survival.
Conclusions
The LTS group lost less blood and required less blood transfusions than the HBPS group. Blood transfusion worsened overall survival. The significantly lower blood transfusion requirement of the LTS group contributes to a potential advantage in their overall survival.
ALTHOUGH LIVER transplantation is an effective treatment for irreversible end-stage liver disease of various causes, it is hindered by the global shortage of cadaveric liver grafts. This shortage drives live donor liver transplantation (LDLT), an operation that addresses this need.1 The estimate of 1% mortality of live liver donors has generated much concern.2-6 The cost paid by these volunteers also includes potentially serious complications such as cholestasis, biliary stricture, portal vein thrombosis,7 and bile leakage.8 In liver graft harvesting, the LDLT surgeon must achieve donor safety and good liver graft function. These goals mandate a thorough knowledge of the liver anatomy and conversance in major hepatectomy without vascular inflow clamping.
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Although it is most prevalent in Asia and Africa,9 the incidence of HCC is rising in western countries.10 An HCC of larger than 5 cm is most reliably treated by tumor extirpation whenever feasible.11,12 During the past 3 decades, hepatectomy for HCC has evolved from a heroic and sanguinary procedure to a controlled, deliberate, and relatively bloodless operation. Nonetheless, it still poses a significant risk with a hospital mortality of 4.5%.11 The risk is expected to be higher for major hepatectomy.13 Although survival is mainly influenced by tumor characteristics,14 treatment outcomes also depend on the surgeon's performance.15 Surgeons in our center share a common philosophy of meticulous dissection with minimal disturbance of the liver housing the HCC. This philosophy is expedited by the anterior approach for right-sided hepatectomy.16 The present study is from a tertiary referral center that provides the services of liver transplantation and the full range of hepatobiliary and pancreatic surgery. It addresses the question of whether the LDLT experience of the surgeon is a factor that influences the outcomes of major hepatectomy for HCC.
Consecutive new patients undergoing major hepatectomy for HCC from January 16, 1996, through December 28, 2001, were included in this single-center study. Major hepatectomy was defined as resection of 3 or more liver segments according to Couinaud's nomenclature.17 Selection criteria for resection included absence of extrahepatic disease and main portal vein tumor thrombus and a satisfactory liver function reserve. Data of patient characteristics, tumor characteristics, and operative findings and outcomes were collected prospectively and entered into an HCC computer database. The surgical team consisted of 7 hepatobiliary and pancreatic surgeons (HBPSs), all competent in performing major hepatectomy independently. The liver transplantation service was primarily provided by 3 of these surgeons. As dictated by the scarcity of cadaveric liver grafts in this region, LDLT was frequently performed.18 These 3 surgeons also perform regular major hepatectomies for primary and metastatic liver cancer. In this study, they were grouped as liver transplantation surgeons (LTSs). The other 4 surgeons, who were not chief LDLT surgeons, constituted the HBPS group.
Major hepatectomies were allocated to each of these 7 surgeons according to the availability of operating rooms and the predetermined operative duties of each surgeon, rather than their backgrounds or track records. All patients underwent the same preoperative evaluation protocol, which included blood biochemisty studies, percutaneous ultrasonography, and computed tomography of the abdomen. In selected patients, hepatic and superior mesenteric angiographies were performed. Liver function was assessed by means of the Child-Pugh grading19 and the indocyanine green clearance test.20
Surgical techniques and postoperative care
Laparotomy was performed via a bilateral subcostal incision with a cephalic midline extension. Intraoperative ultrasonography was performed to determine whether the disease was operable and the extent of HCC involvement and to guide transection. The transection plane was then marked on the liver capsule by means of cautery. Hepatic parenchymal transection was performed using an ultrasonic surgical aspirator (Cavitron Ultrasonic Surgical Aspirator; Valleylab, Boulder, Colo).21 Venacaval branches were individually ligated or clipped and then divided. All patients received the same postoperative care by the same team of surgeons in this study. Patients were treated in the intensive care unit during the early postoperative course. Parenteral nutritional support was provided for patients with liver cirrhosis.22 Early enteric nutrition was started once bowel activity returned. Discharge from the hospital was decided according to the clinical state.
The primary end point was overall survival, calculated from the date of the major hepatectomy. The secondary end point was disease-free survival. We assessed perioperative outcomes, including blood loss, blood transfusion, and complications. The patients were followed up monthly for 6 months and then every 3 months at the outpatient clinic. Follow-up assessments included physical assessment, serum biochemistry studies, and measurement of serum α-fetoprotein level. Computed tomography was repeated every 3 months for the first 2 years and then every 6 months. Tumor recurrence was assessed on the basis of computed tomography findings and serum α-fetoprotein level.
Data were recorded prospectively in a computerized database by a single research assistant. We prospectively recorded all intraoperative and postoperative complications. Hospital death was defined as death during the hospital stay for the hepatic resection. We calculated disease-free survival from the date of hepatic resection to the date when recurrence was diagnosed. We compared groups on an intention-to-treat basis. Continuous variables were expressed as mean ± SD or median and range as appropriate. We compared categorical variables by the χ2 test or the Fisher exact test, and continuous variables by means of the Mann-Whitney test. Survival analysis, including overall and disease-free survival, was estimated by the Kaplan-Meier survival method. Overall survival was calculated from the time of major hepatectomy to the date of death or the time of analysis. We analyzed statistical comparison of survival distribution by log-rank tests. Hospital death was included in the analysis of overall survival, but was excluded from the analysis of disease-free survival. We used multivariate analysis by the Cox proportional hazards regression model to identify independent prognostic factors and to predict the overall cumulative survival. We considered P<.05 to indicate statistical significance. We used SPSS for Windows, Version 10.0 (SPSS Inc, Chicago, Ill), to perform statistical analyses.
Baseline clinicopathologic characteristics
During the 6-year study period, 250 consecutive new patients underwent major hepatectomies at the Department of Surgery, The University of Hong Kong Medical Center, Queen Mary Hospital, Hong Kong, People's Republic of China. We divided the hepatectomies between the LTS (n = 102 hepatectomies) and HBPS groups (n = 148 hepatectomies). The number of major hepatectomies performed per surgeon ranged from 19 to 76. During the same period, 77 cadaveric donor liver transplantations and 107 LDLTs (89 right lobe, 3 left lobe, and 15 left lateral segment) were performed. The 2 groups were well balanced with regard to the baseline characteristics, as shown in Table 1. Most patients were male, with a mean age of 52.3 ± 2.3 and 53.5 ± 12.8 years for the LTS and HBPS groups, respectively. More than 80% of the patients had positive findings for the hepatitis B surface antigen. None of them had Child-Pugh grade C disease. The mean hemoglobin levels were within the reference range at 13.4 ± 1.7 and 13.7 ± 1.8 g/dL for the LTS and HBPS groups, respectively. The mean size of the primary liver lesion was similar (8.4 ± 4.6 and 8.3 ± 4.5 cm for the LTS and HBPS groups, respectively) (Table 2). Most livers had chronic hepatitis and cirrhosis. The extent of hepatectomy in both groups of patients is listed in Table 3. Hepatic resection appeared more extensive in the LTS than in the HBPS group, as significantly more combined segment I (caudate lobe) resections were performed (15/102 and 6/148, respectively; P = .006). Although technically demanding, segment I resection is still a safe procedure.25
The intraoperative and postoperative data are listed in Table 4. Mean blood loss was less in the LTS group (1.36 ± 1.37 vs 2.21 ± 2.40 L; P<.001). Mean blood transfusion was only 0.27 ± 0.82 L in the LTS group compared with 0.51 ± 0.94 L in the HBPS group (P = .001). A smaller proportion of the LTS group required blood transfusion (17/102 [16.7%] vs 57/148 [38.5%]; P<.001). The duration of operation was comparable between the 2 groups, as were the mean tumor-free resection margins. About 5% of the patients in each group had a positive resection margin. Rupture of tumor during resection was uncommon (7.8% and 12.8% for the LTS and HBPS groups, respectively). There were 7 hospital deaths in each group (6.9% and 4.7% for the LTS group and HBPS group, respectively; P = .47). The rate of surgical complications such as bile duct injury was comparable in both groups at approximately 2%. The median hospital stay was 2 days fewer for the LTS than the HBPS groups (11 vs 13 days), although the difference was not statistically significant.
Long-term survival results
Difference in median survival was not demonstrable (45.5 and 44.7 months for the LTS and HBPS groups, respectively). The estimated 1-, 3-, and 5-year survival rates were 74.6%, 55.3%, and 44.6%, respectively for the LTS group, and 75.3%, 55.3%, and 40.9%, respectively, for the HBPS group. The median disease-free survival for the LTS and HBPS groups was 12.7 and 15.6 months, respectively. Disease-free survival at 1, 3, and 5 years was 51.6%, 34.8%, and 24.0%, respectively, for the LTS group and 55.1%, 37.3%, and 28.0%, respectively, for the HBPS group. The overall and disease-free survival rates of the 2 groups showed no statistically significant difference (Figure 1 and Figure 2).
Among the 250 patients, 74 (29.6%) required blood transfusion. There was a tendency of better overall survival in those who did not receive transfusion. The median overall survival of patients who did not have blood transfusion was 55.8 months, whereas those who had transfusion was 34.3 months (P = .06) (Figure 3). The 1-, 3-, and 5-year overall survival rates were 79.6%, 58.3%, and 48.0%, respectively, for the nontransfused group and 65.5%, 45.9%, and 33.8%, respectively, for the transfused group. The disease-free survival was also longer in the nontransfused group than in the transfused group (median survival, 16.1 vs 12.4 months), although the difference did not reach a statistical significance (P = .25) (Figure 4).
Variables that might affect the overall and disease-free survivals (ie, surgeon group, hepatitis status, cirrhosis, tumor size, vascular invasion, blood loss volume, blood transfusion, and positive resection margin) were subjected to Cox regression analysis. The hazard ratios, confidence intervals, and probability values for the multivariate model are listed in Table 5. Transfusion, cirrhosis, and venous invasion were strong independent predictors of a decreased overall survival. Venous invasion was the most significant factor, with a relative risk of 2.77. Transfusion, however, was not a risk factor in compromising disease-free survival. Venous invasion with a relative risk of 2.33 worsened disease-free survival. Cirrhosis followed by tumor size were independent predictors for poor disease-free survival. The Cox model did not show the surgeon as an independent factor that influenced survival.
Hepatic resection has been the mainstay of surgical treatment of HCC. Small HCC in a liver of poor reserve can be resected by means of a wedge excision. For unresectable small HCC (≤5 cm) in patients with decompensated Child-Pugh class B or C cirrhosis, liver transplantation is the preferred option,26,27 as long-term survival is offset by later deterioration of liver function and recurrent HCC.28 A large HCC contraindicates liver transplantation, as the size is a strong predictor of microvascular invasion, which preludes tumor dissemination.29 In the past 2 decades, suboptimal preoperative liver function, massive intraoperative bleeding, postoperative septic complications, and hepatic failure were identified as the chain of events leading to hospital death in patients undergoing hepatectomy for HCC. Therefore, we have focused on the following: (1) the preoperative evaluation of hepatic function to select patients with adequate hepatic functional reserve for hepatectomy; (2) surgical techniques to reduce intraoperative bleeding; (3) avoidance of ischemic injury to the liver remnant and biliary leakage; and (4) promotion of liver function in the postoperative period.
Live donor liver transplantation can be considered the ultimate surgery for the liver. Adult-to-adult LDLT consists of total hepatectomy for the recipient and partial hepatectomy for the donor. The latter procedure may or may not include the middle hepatic vein. Isolation and preparation of vessels of the recipient and donor require meticulous dissection and anticipation of anatomical variations. Vascular anastomosis also demands careful control of vessels. Technical difficulties at times need interpositional vascular grafts for reconstruction. Innovation and refinement in the harvesting techniques of the liver graft from the live donor were made in the past decade.30-32 Intraoperative ultrasonography navigates a precise line of transection.16 The exposure of the abdomen, exploration of the liver, knowledge about the tolerance of the liver for ischemia, and techniques of ex situ resection demonstrate the close ties between liver transplantation and hepatectomy.
In this study, the LTS group demonstrated better outcomes in terms of less blood loss and transfusion requirements. These are the objectives of an LDLT program that ensure the safety and well-being of the live liver donor. However, we found no difference in survival between the patients undergoing operation by the different surgeon groups. Nonetheless, survival tended to improve in those who did not receive blood transfusion. As the percentage of patients in the LTS group who underwent blood transfusion was lower than those in the HBPS group (16.7% vs 38.5%), a survival benefit in the LTS group is expected. Increased perioperative blood transfusion has been reported to increase the chance of recurrence,33,34 especially for large HCC.35,36 Reports have also shown that no association exists between blood transfusion and disease-free recurrence.37,38 Blood transfusion has never been reported as a factor with survival benefits, which might be the result of publication bias. Blood transfusion in this study did not emerge as a very significant factor because, unlike previous series, the volume of blood loss in this study was not large. This may be explained by the fact that the 7 surgeons were cautious and vigilant in reducing the need for blood transfusion; other nontechnical factors therefore appeared significant. This finding was reassuring, as the comparison was performed within a single center. Factors such as venous invasion and cirrhosis compromised survival at an extent that overwhelmed the effect of blood transfusion. With respect to the tumor, blood transfusion may only affect the survival of patients with early HCC who underwent hepatectomy. A study of a larger number of patients may also allow comparison between 2 groups with stratification according to each statistically significant prognostic factor.
The setup of liver surgery centers is different around the world. In European and Asian centers, a mixture of liver transplantation and hepatic resection cases is common. In the United States, centers often exclusively provide 1 of these 2 subspecialties. This brings up the issue of flexibility and diversity vs specialization, ie, would patients requiring major hepatectomy benefit from surgeons who also provide liver transplantation? This is a difficult question to answer, as studies on health care providers are often more difficult to conduct than those on health care receivers, owing to the smaller number of the former and other confounding factors such as reluctance of self-reporting. The data from the present study suggest that superspecialization in 1 particular area of liver surgery may not be desirable. Unity in hepatobiliary and pancreatic surgery with cross-fertilization between highly specialized disciplines can only benefit the patient. Versatility of surgeons also allows for a flexible service. Transplantation is often regarded as an extension of the HCC service for patients with cirrhosis or as a salvage procedure for recurrence of HCC. This setup also allows for better continuity of care.
Experience has a positive influence on the results of surgical treatment. Hence, what are the attributes of an elite hepatectomist? In a center that provides liver transplantation on an average of 1 case per week, the surgeons responsible for liver transplantation were analyzed as a single group. Their results of major hepatectomy for HCC were compared with those of the surgeons who were not intimately or ultimately responsible for patients undergoing liver transplantation. A statistically significant difference in overall and disease-free survival was not demonstrated. One could argue that the standard of service is already above the standard that might influence survival. Liver transplantation started to flourish in Asia in the early 1990s. The technical complexities and ingenuity required by the procedure allow only the most skillful surgeons to perform it. Is the selection process of surgeons or their training more crucial? Perhaps this question will never be answered, since a field trial to compare surgeons who start with hepatic resections followed by specialization in liver transplantation and those who receive training on hepatic resections only is inconceivable.
Live donor liver transplantation is built on the solid experience of major hepatic resection,39 which also nurtures experience in vascular control during major hepatectomy.40 In tandem, the 2 procedures play complementary roles in patient care. As the first of a kind, studies from centers with a similar setup can affirm this view. For centers with an established LDLT program in place, instead of gaining experience from hepatectomy for malignancies without vascular clamping,41 donor hepatectomy can be learned by assisting and operating under the guidance of experienced LDLT surgeons. As a result of the rise in the demand for LDLT, surgeons of the HBPS group in the present study have started to participate, under guidance, in LDLT as chief surgeons since early 2002, when this study was finished. A prospective examination of the results achieved by these future chimeric surgeons would be informative.
In major hepatectomy for HCC, this study did not show that the surgeon's LDLT experience has a positive influence on the overall and disease-free survival of the patients. Nonetheless, the LTS group had less blood loss and required less blood transfusion. In the 250 patients of this series, multivariate analysis showed that blood transfusion had worsened overall survival. As the blood transfusion requirement of the patients in the LTS group was significantly lower, there is a potential advantage in the overall survival.
Corresponding author and reprints: See-Ching Chan, FRACDS, FRCS(Edin), Department of Surgery, The University of Hong Kong, 102 Pokfulam Rd, Hong Kong, People's Republic of China (e-mail: seechingchan@hotmail.com).
Accepted for publication October 19, 2002.
2.Trotter
JFWachs
MEverson
GTKam
I Adult-to-adult transplantation of the right hepatic lobe from a living donor.
N Engl J Med. 2002;3461074- 1082
Google ScholarCrossref 3.Cronin II
DCMillis
JMSiegler
M Transplantation of liver grafts from living donors into adults: too much, too soon.
N Engl J Med. 2001;3441633- 1637
Google ScholarCrossref 5.Malago
MBurdelski
MBroelsch
CE Present and future challenges in living related liver transplantation.
Transplant Proc. 1999;311777- 1781
Google ScholarCrossref 6.Strong
RW Whither living donor liver transplantation [editorial]?
Liver Transpl Surg. 1999;5536- 538
Google ScholarCrossref 7.Fan
STLo
CMLiu
CLYong
BHChan
JKNg
IO Safety of donors in live donor liver transplantation using right lobe grafts.
Arch Surg. 2000;135336- 340
Google ScholarCrossref 8.Fujita
SKim
IDUryuhara
K
et al. Hepatic grafts from live donors: donor morbidity for 470 cases of live donation.
Transpl Int. 2000;13333- 339
Google ScholarCrossref 10.El Serag
HBMason
AC Rising incidence of hepatocellular carcinoma in the United States.
N Engl J Med. 1999;340745- 750
Google ScholarCrossref 11.Fong
YSun
RLJarnagin
WBlumgart
LH An analysis of 412 cases of hepatocellular carcinoma at a Western center.
Ann Surg. 1999;229790- 799
Google ScholarCrossref 12.Colella
GBottelli
RDe Carlis
L
et al. Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization.
Transpl Int. 1998;11
((suppl 1))
S193- S196.
Google ScholarCrossref 13.Pol
BCampan
PHardwigsen
JBotti
GPons
JLe Treut
YP Morbidity of major hepatic resections: a 100-case prospective study.
Eur J Surg. 1999;165446- 453
Google ScholarCrossref 14.Poon
RTFan
STNg
IOLo
CMLiu
CLWong
J Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma.
Cancer. 2000;89500- 507
Google ScholarCrossref 15.Fan
STNg
IOPoon
RTLo
CMLiu
CLWong
J Hepatectomy for hepatocellular carcinoma: the surgeon's role in long-term survival.
Arch Surg. 1999;1341124- 1130
Google ScholarCrossref 16.Liu
CLFan
STLo
CMTung-Ping
PRWong
J Anterior approach for major right hepatic resection for large hepatocellular carcinoma.
Ann Surg. 2000;23225- 31
Google ScholarCrossref 17.Couinaud
C Liver anatomy: portal (and suprahepatic) or biliary segmentation.
Dig Surg. 1999;16459- 467
Google ScholarCrossref 18.Liu
CLFan
STLo
CMYong
BHFung
ASWong
J Right-lobe live donor liver transplantation improves survival of patients with acute liver failure.
Br J Surg. 2002;89317- 322
Google ScholarCrossref 19.Pugh
RNMurray-Lyon
IMDawson
JLPietroni
MCWilliams
R Transection of the oesophagus for bleeding oesophageal varices.
Br J Surg. 1973;60646- 649
Google ScholarCrossref 20.Fan
STLai
ECLo
CMNg
IOWong
J Hospital mortality of major hepatectomy for hepatocellular carcinoma associated with cirrhosis.
Arch Surg. 1995;130198- 203
Google ScholarCrossref 21.Fan
STLai
ECLo
CMChu
KMLiu
CLWong
J Hepatectomy with an ultrasonic dissector for hepatocellular carcinoma.
Br J Surg. 1996;83117- 120
Google ScholarCrossref 22.Fan
STLo
CMLai
ECChu
KMLiu
CLWong
J Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma.
N Engl J Med. 1994;3311547- 1552
Google ScholarCrossref 23.American Joint Commission on Cancer, AJCC Cancer Staging Manual. 5th ed. Philadelphia, Pa Lippincott-Raven Publishers1997;109- 111
24.Couinaud
C Etudes Anatomiques et Chirurgicales. Paris, France Masson & Cie1957;
25.Nagasue
NKohno
HYamanoi
A
et al. Resection of the caudate lobe of the liver for primary and recurrent hepatocellular carcinomas.
J Am Coll Surg. 1997;1841- 8
Google Scholar 26.Mazzaferro
VRegalia
EDoci
R
et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.
N Engl J Med. 1996;334693- 699
Google ScholarCrossref 27.Mor
EKaspa
RTSheiner
PSchwartz
M Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation.
Ann Intern Med. 1998;129643- 653
Google ScholarCrossref 28.Dmitrewski
JEl Gazzaz
GMcMaster
P Hepatocellular cancer: resection or transplantation.
J Hepatobiliary Pancreat Surg. 1998;518- 23
Google ScholarCrossref 29.Esnaola
NFLauwers
GYMirza
NQ
et al. Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation.
J Gastrointest Surg. 2002;6224- 232
Google ScholarCrossref 30.Fan
STLo
CMLiu
CL Technical refinement in adult-to-adult living donor liver transplantation using right lobe graft.
Ann Surg. 2000;231126- 131
Google ScholarCrossref 31.Imamura
HMakuuchi
MSakamoto
Y
et al. Anatomical keys and pitfalls in living donor liver transplantation.
J Hepatobiliary Pancreat Surg. 2000;7380- 394
Google ScholarCrossref 32.Tanaka
KKiuchi
T Living-donor liver transplantation in the new decade: perspective from the twentieth to the twenty-first century.
J Hepatobiliary Pancreat Surg. 2002;9218- 222
Google ScholarCrossref 33.Yamamoto
JKosuge
TTakayama
T
et al. Perioperative blood transfusion promotes recurrence of hepatocellular carcinoma after hepatectomy.
Surgery. 1994;115303- 309
Google Scholar 34.Makino
YYamanoi
AKimoto
TEl Assal
ONKohno
HNagasue
N The influence of perioperative blood transfusion on intrahepatic recurrence after curative resection of hepatocellular carcinoma.
Am J Gastroenterol. 2000;951294- 1300
Google ScholarCrossref 35.Hanazaki
KKajikawa
SShimozawa
N
et al. Hepatic resection for large hepatocellular carcinoma.
Am J Surg. 2001;181347- 353
Google ScholarCrossref 36.Lauwers
GYVauthey
JN Pathological aspects of hepatocellular carcinoma: a critical review of prognostic factors.
Hepatogastroenterology. 1998;45
((suppl 3))
1197- 1202
Google Scholar 37.Matsumata
TIkeda
YHayashi
HKamakura
TTaketomi
ASugimachi
K The association between transfusion and cancer-free survival after curative resection for hepatocellular carcinoma.
Cancer. 1993;721866- 1871
Google ScholarCrossref 38.Kwon
AHMatsui
YKamiyama
Y Perioperative blood transfusion in hepatocellular carcinomas: influence of immunologic profile and recurrence free survival.
Cancer. 2001;91771- 778
Google ScholarCrossref 39.Lo
CMFan
STLiu
CL
et al. Extending the limit on the size of adult recipient in living donor liver transplantation using extended right lobe graft.
Transplantation. 1997;631524- 1528
Google ScholarCrossref 40.Erhard
JEigler
FW Effect of liver transplantation on general techniques of liver resection [in German].
Chirurg. 1996;67331- 340
Google Scholar 41.Robles
RRamirez
PBueno
FS
et al. Importance of training in liver resection surgery to implement programs of living donor liver transplantation.
Transplant Proc. 2002;34240
Google ScholarCrossref